Vasorelaxant effects of 2-nitro-1-phenyl-1-propanol in rat aorta

• Published in: Clinical and experimental pharmacology & physiology Vol. 43; no. 11; pp. 1054 - 1061
• Main Authors: de Brito, Teresinha Silva, Batista-Lima, Francisco José, Gadelha, Kalinne Kelly Lima, da Fonseca-Magalhães, Patrícia Andrea, Lahlou, Saad, Magalhães, Pedro Jorge Caldas
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.11.2016; Wiley Subscription Services, Inc
• Subjects: Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; cyclic nucleotides; Dose-Response Relationship, Drug; Male; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; nitro compounds; Nitro Compounds - pharmacology; norephedrine; Organ Culture Techniques; Propanols - pharmacology; Rats; Rats, Wistar; vascular smooth muscle; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - pharmacology; cyclic nucleotides; nitro compounds; vascular smooth muscle; norephedrine
• DOI: 10.1111/1440-1681.12625
• ISSN: 0305-1870

Summary 2‐Nitro‐1‐phenyl‐1‐propanol (NPP) is a nitro alcohol that is known as an intermediate in the synthesis of sympathomimetic agents, such as norephedrine. The present study investigated the vasoactive effects of NPP on rat aorta. In endothelium‐intact aortic rings, NPP fully relaxed contractions that were induced by phenylephrine, KCl, and U‐46619. The relaxant effects of NPP on phenylephrine‐elicited contractions remained unaffected by NG‐nitro‐l‐arginine methyl ester (l‐NAME), indomethacin, propranolol, tetraethylammonium, 4‐aminopyridine, and glibenclamide. Conversely, pretreatment with 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), cis‐N‐(2‐phenylcyclopentyl)‐azacyclotridec‐1‐en‐2‐amine hydrochloride (MDL‐12,330A), and N‐[2‐(P‐bromocinnamylamino)ethyl]‐5‐isoquinolinesulfonamide dihydrochloride (H‐89) reduced the ability of NPP to relax contractions that were elicited by phenylephrine. NPP inhibited the vasoconstrictor response that was induced by Ca2+ in aortic rings that were stimulated by pharmacomechanical or electromechanical coupling with phenylephrine and 60 mmol/L KCl, respectively, and after the depletion of intracellular Ca2+ stores. Such effects of NPP were significantly reversed by pretreatment with the guanylyl cyclase inhibitor ODQ and weakly influenced by the adenylyl cyclase inhibitor MDL‐12,330A. In Ca2+‐free medium, NPP inhibited transient contractions that were induced by phenylephrine but not caffeine. In homogenates of aortic rings, NPP increased cyclic guanosine 3′,5′‐monophosphate (cGMP) and cyclic adenosine 3′‐5′‐monophosphate levels, but this effect was statistically significant only for cGMP. In conclusion, in contrast to the vasoconstrictor amine norephedrine, NPP is a vasodilator in rat aorta, and its relaxant effects are likely attributable to cGMP production.